Controlled Drug Release from the Aggregation–Disaggregation Behavior of pH-Responsive Microgels

In this submission, two independent sets of microgels were synthesized that exhibit pH responsivity over different solution pH ranges. The microgels were synthesized by copolymerizing two different comonomers with poly(N-isopropylacrylamide) (pNIPAm). The microgels copolymerized with acrylic acid exhibit a negative charge above pH 4.25, while the microgels copolymerized with N-[3-(dimethylamino)propyl]methacrylamide exhibit a positive charge below pH 8.4; these microgels are neutral outside of these pH ranges. We show that aggregates form when the two independent sets of microgels are exposed to one another in a solution that renders them both charged. Furthermore, in solutions of pH outside of this range, the microgels disaggregate because one of the microgels becomes neutralized. This behavior was exploited to load (aggregation) and release (disaggregation) a small-molecule model drug, methylene blue. This aggregate-based system is one example of how pNIPAm-based microgels can be used for controlled/triggered drug delivery, which can have implications for therapeutics.